Impact of 1-year treatment with dupilumab on work productivity in Japanese patients with atopic dermatitis.

Atopic dermatitis (AD) places a burden on work productivity. Recently, dupilumab was approved for AD, but its impact on work productivity in Japanese patients has not been reported. Furthermore, data on the effect of long-term treatment with dupilumab on work productivity are limited. We investigated the work productivity and activity in Japanese patients with moderate-to-severe AD, utilizing the Japanese version of the Work Productivity and Activity Impairment (WPAI-AD-Japan) questionnaire. Furthermore, we examined the impact of dupilumab on work productivity. Adult moderate-to-severe AD patients treated with dupilumab for more than 12 months from March 2020 to June 2022 who filled out the WPAI-AD-Japan questionnaire were included. Twenty-eight adult AD patients were analysed. Absenteeism was low (mean: 5.3%), but presenteeism, work productivity loss and activity impairment were high (36.8%, 39.7%, 48.9%, respectively). Significant positive correlations were observed between work productivity loss and visual analogue scale (VAS) score of pruritus and between activity impairment and dermatology life quality index (DLQI). Dupilumab treatment significantly reduced presenteeism, work productivity loss and activity impairment at both 6 and 12 months. The extent of their amelioration was numerically higher at 12 months than at 6 months. The reduction rates in presenteeism, work productivity loss and activity impairment were positively correlated with the reduction rates in DLQI and VAS score of pruritus at 12 months. Dupilumab improved work productivity in Japanese AD patients. Long-term remission of pruritus and improved quality of life are important for comprehensive improvement of work productivity.

Expression of interleukin-36 receptor antagonist in a patient with generalized pustular psoriasis harboring the p.Pro82Leu variant in the IL36RN gene.

It has recently been revealed that mutation of the IL36RN gene contributes to the development of generalized pustular psoriasis (GPP). The IL36RN gene encodes interleukin (IL)-36 receptor antagonist (IL-36Ra), which has antagonistic roles against IL-36α, -36ß, and -36γ. Previously, sanger sequencing performed in 62 Chinese GPP patients to identify IL36RN mutations revealed a new variant, c.245C>T (p.Pro82Leu), in a single heterozygous state in a patient with adult-onset GPP with psoriasis vulgaris. Since this p.Pro82Leu variant was not found in the psoriasis vulgaris or control groups in their study, they speculated that this variant might lead to exacerbated inflammatory responses. Meanwhile, Sorting Intolerant From Tolerant and PolyPhen-2, pathogenicity prediction tools, predict this variant as tolerated and benign. To date, its pathogenicity is unknown. We experienced a patient with GPP harboring the p.Pro82Leu variant, and investigated mRNA and protein expressions of IL-36Ra. Polymerase chain reaction conducted on hair follicle samples obtained from the scalp of the patient with GPP harboring the p.Pro82Leu using primers to detect mRNA of exons 2 and 5 in IL36RN demonstrated mRNA expression of IL36RN. Immunohistochemical staining revealed IL-36Ra expression in the keratinocytes of the patient with GPP harboring the p.Pro82Leu as in those of a GPP patient without the mutation (positive control). Furthermore, quantitative analysis of the immunofluorescent staining by ImageJ revealed that the expression level of IL-36Ra in the keratinocytes of the patient with GPP harboring p.Pro82Leu was higher than that in the healthy control and not lower than that in the GPP patients without the mutation. Our results indicate no aberrant splicing in this variant. In addition, according to the 1000 Genomes Project, this variant could be a founder mutation. Considering these factors together, this variant is unlikely to be associated with the development of GPP.

Apremilast downregulates interleukin-17 production and induces splenic regulatory B cells and regulatory T cells in imiquimod-induced psoriasiform dermatitis.

BACKGROUND: Apremilast, a selective inhibitor of the enzyme phosphodiesterase 4, is efficacious for psoriasis. However, detailed in vivo effects of apremilast on psoriasis remain to be elucidated. OBJECTIVE: To examine the in vivo effects of apremilast on psoriasis. METHODS: Psoriasiform dermatitis was induced by applying imiquimod (IMQ) on the murine shaved back skin for six days. Mice were treated with apremilast or vehicle intraperitoneally daily. RESULTS: Apremilast alleviated IMQ-induced psoriasiform dermatitis clinically and pathologically on days 3-6 by reducing infiltration of antigen-presenting cells and interleukin (IL)-17A-positive cells and increasing infiltration of Foxp3-postive cells into the skin on day 6, although a significant increase in IL-10 mRNA level was not observed on day 2. In addition, mRNA expression of IL-17A, IL-17F, and IL-22 was lower in the skin of IMQ-applied mice treated with apremilast than in those without apremilast on day 2, and apremilast inhibited infiltration of IL-17A-producing γδ T cells into the dermis on day 6. Furthermore, apremilast induced regulatory T cells and regulatory B cells in the spleen but not in the draining lymph nodes. CONCLUSION: Apremilast downregulated IL-17 production and induced splenic regulatory B cells and regulatory T cells in an IMQ-induced psoriasiform dermatitis mouse model.